Wound Repair and Regeneration最新文献

This meta-analysis aimed to systematically assess and synthesise healing rates within a 12- to 24-week treatment period among patients with diabetic foot ulcers receiving standard-of-care interventions in randomised controlled trials. This meta-analysis included 32 randomised controlled trials conducted between 1996 and 2023, with sample sizes ranging from 9 to 169 patients. A random-effects model was applied to estimate pooled healing and infection rates. Heterogeneity was quantified using the I² statistic, and publication bias was assessed using Egger's test. The results revealed a pooled healing rate of 33.15% with a 95% confidence interval (CI) of 31.18%-35.11% and an average healing time of approximately 50.14 days (standard deviation: 31.10 days). The infection proportion was determined to be 17.4% (95% CI: 12.2%-22.5%). Subgroup analysis indicated marginally higher healing rates in the 'Saline Gauze' group compared to the 'Alginate' group, although the latter exhibited a reduced infection proportion. Sensitivity analysis affirmed the robustness of these findings whereas Egger's test suggested the presence of potential publication bias concerning the healing outcomes. The standard-of-care interventions for diabetic foot ulcers demonstrate limited effectiveness, with only about one-third of patients achieving wound closure. The significant heterogeneity and publication bias observed necessitate a cautious interpretation of these results. The findings highlight the need for advanced wound care strategies and personalised treatment plans to improve outcomes in diabetic foot ulcers management. Future research should focus on conducting high-quality, well-reported randomised controlled trials to better understand effective treatments for DFUs.

Bacterial biofilms represent a formidable challenge in the treatment of chronic wounds, largely because of their resistance to conventional antibiotics. The emergence of multidrug-resistant (MDR) bacterial strains exacerbates this issue, necessitating a shift towards exploring alternative therapeutic approaches. In response to this urgent need, there has been a surge in research efforts aimed at identifying effective non-antibiotic treatments. Recently noted among the non-antibiotic options are selective serotonin reuptake inhibitors (SSRIs) and beta-adrenergic (β-AR) antagonists. Both have demonstrated antimicrobial activities and wound-healing properties, which makes them particularly promising potential therapeutics for chronic wounds. This review seeks to comprehensively evaluate the landscape of non-antibiotic strategies for managing wound infections. By analysing the latest research findings and clinical developments, it aims to shed light on emerging therapeutic alternatives. Additionally, the review delves into the potential of repurposing systemic therapeutics for topical application, offering insights into the feasibility and challenges associated with current approaches. We also address the necessity of translating promising preclinical results into tangible clinical benefits.

Traditional wound dressings, despite their widespread use, face limitations, such as poor infection control and insufficient healing promotion. To address these challenges, bioactive materials have emerged as a promising solution in wound care. This comprehensive review explores the latest developments in wound healing technologies, starting with an overview of the importance of effective wound management, emphasising the need for advanced bioactive wound dressings. The review further explores various bioactive materials, defining their characteristics. It covers a wide range of natural and synthetic biopolymers used to develop bioactive wound dressings. Next, the paper discusses the incorporation of bioactive agents into wound dressings, including antimicrobial and anti-inflammatory agents, alongside regenerative components like growth factors, platelet-rich plasma, platelet-rich fibrin and stem cells. The review also covers fabrication techniques for bioactive wound dressings, highlighting techniques like electrospinning, which facilitated the production of nanofibre-based dressings with controlled porosity, the sol-gel method for developing bioactive glass-based dressings, and 3D bioprinting for customised, patient-specific dressings. The review concludes by addressing the challenges and future perspectives in bioactive wound dressing development. It includes regulatory considerations, clinical efficacy, patient care protocol integration and wound healing progress monitoring. Furthermore, the review considers emerging trends such as smart materials, sensors and personalised medicine approaches, offering insights into the future direction of bioactive wound dressing research.

The WOUND-Q is a patient-reported outcome measure for individuals with any type of chronic wound. This study aimed to identify patient and wound factors associated with the four WOUND-Q health-related quality of life (HRQL) scales: Life impact, Psychological, Sleep, and Social. Adults with a chronic wound were recruited internationally through clinical settings between August 2018 and May 2020, and through an online platform (i.e. Prolific) in September 2022. Multivariable linear regression analyses were conducted to identify factors significantly associated with the WOUND-Q scales. The assessments obtained were 1273, 1275, 706, and 1256 for the Life Impact, Psychological, Sleep, and Social scales, respectively. The mean age of participants was 55 (SD = 18) years; most (66%) had a single wound, and most (56%) wounds had lasted more than 6 months. The most common causes were trauma, surgery, and diabetic foot ulcer. Wound characteristics associated with worse scores on at least one of the scales were drainage, vacuum treatment, aetiologies (i.e. diabetic foot ulcer, trauma, other, multiple), duration (i.e. 10-11 months), having four or more wounds, smell, and sleep interference, while wound location different from the face or neck was associated with better scores (p < 0.05). Patient factors associated with worse scores included having diabetes or a comorbidity, whereas increasing age or male gender were associated with better scores (p < 0.05). Sleep disturbances had the largest negative influence on HRQL scores. This study identified factors affecting HRQL in individuals with chronic wounds. Understanding these associations can inform better management and treatment strategies to improve HRQL for these patients.

Bacterial colonisation in hypertrophic scars (HSs) has been reported, yet the precise mechanism of their contribution to scar formation remains elusive. To address this, we examined HS and normal skin (NS) tissues through Gram staining and immunofluorescence. We co-cultured fibroblasts with heat-inactivated Staphylococcus aureus (S. aureus) and evaluated their levels of apoptosis and proliferation by flow cytometry and Cell Counting Kit-8 assay, respectively. Additionally, we performed proteomic analysis and western blotting to identify upregulated proteins. To assess autophagy levels, we examined light chain 3 (LC3) expression through western blotting and immunofluorescence, and transmission electron microscopy (TEM) was performed to detect autophagy-associated vesicles. Our results demonstrated a notable increase in bacterial load, primarily S. aureus, in HS tissues. Furthermore, S. aureus promoted fibroblast proliferation and enhanced the expression of profibrotic markers such as transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), collagen I, collagen III and α smooth muscle actin (α-SMA). Proteomic analysis highlighted heat shock factor-binding protein 1 (HSBP1) as a key upregulated protein mediating the profibrotic effects induced by S. aureus. Knockdown of HSBP1 reversed these effects. Intriguingly, HSBP1 also upregulated LC3 and Beclin-1 expression and increased the number of autophagosomes in fibroblasts. Finally, when fibroblasts stimulated by S. aureus were treated with HSBP1 siRNA, autophagy levels decreased significantly. Collectively, our findings suggest that S. aureus, via HSBP1, stimulates fibroblast proliferation and promotes their transition into myofibroblasts, triggering autophagy and fibrosis. These results underscore the potential of HSBP1 as a therapeutic target for the management of HSs.

The objective of this systematic review was to synthesise the evidence of the impact of pressure injuries (PIs) on the health-related quality of life (HRQoL) of adults aged 18 years and older. Electronic databases (Ovid Medline, Ovid Embase, CINAHL EBSCO, Scopus and Central Register of Controlled Trials) were searched for eligible studies published between January 2019 and April 2024. All identified articles were reviewed by two reviewers against the eligibility criteria. The risk of bias was assessed using the Mixed Methods Appraisal Tool and the Joanna Briggs Institute critical appraisal tool. Data were narratively synthesised due to methodological heterogeneity. Twenty-two studies (12 quantitative; 9 qualitative;1 mixed methods) met the inclusion criteria. The qualitative studies were grouped into four impact areas: symptoms, physical function, psychological well-being and social functioning. Five instruments were used to assess HRQoL and identified low scores in people with PIs, with the lowest scores mostly reported in physical functioning and role physical and emotional concepts. A complexity of factors influenced theHRQoL of people with PI. This review synthesised both quantitative and qualitative evidence indicating PI was associated with low HRQoL scores and negatively affected all aspects of HRQoL. This review emphasised the complexity of factors related to PI and its impact on HRQoL. Further emphasis on the impact of the complexity of factors on HRQoL of people with PI should be considered in future studies.

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.

Preclinical studies for wound healing disorders are an essential step in translating discoveries into therapies. Also, they are an integral component of initial safety screening and gaining mechanistic insights using an in vivo approach. Given the complexity of the wound healing process, existing guidelines for animal testing do not capture key information due to the inevitable variability in experimental design. Variations in study interpretation are increased by complexities associated with wound aetiology, wounding procedure, multiple treatment conditions, wound assessment, and analysis, as well as lack of acknowledgement of limitation of the model used. Yet, no standards exist to guide reporting crucial experimental information required to interpret results in translational studies of wound healing. Consistency in reporting allows transparency, comparative, and meta-analysis studies and avoids repetition and redundancy. Therefore, there is a critical and unmet need to standardise reporting for preclinical wound studies. To aid in reporting experimental conditions, The Wound Reporting in Animal and Human Preclinical Studies (WRAHPS) Guidelines have now been created by the authors working with the Wound Care Collaborative Community (WCCC) GAPS group to provide a checklist and reporting template for the most frequently used preclinical models in support of development for human clinical trials for wound healing disorders. It is anticipated that the WRAHPS Guidelines will standardise comprehensive methods for reporting in scientific manuscripts and the wound healing field overall. This article is not intended to address regulatory requirements but is intended to provide general guidelines on important scientific considerations for such studies.

Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, which is a major driver of mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared to mechanical injury. Here, we investigate keratinocyte behaviour following burn injury and the subsequent potential for microbial colonisation of burn wounds over time. Real-time imaging, coupled with tracking of photoconverted cells, revealed that early keratinocyte motility contributes to the spread of epithelial damage beyond the initial site of burn injury and that increased epithelial damage was associated with wound colonisation by the fungal pathogen Candida albicans. Modulating osmotic balance by treating larval zebrafish with isotonic medium limited the spread of epithelial damage and reduced microbial colonisation of burn wounds. Using cultured human skin, we found that topical treatment with isotonic solution (saline) similarly prevented the spread of epithelial damage over time. These findings indicate that keratinocyte behaviour contributes to burn wound progression in larval zebrafish and links keratinocyte dynamics to microbial colonisation of burn wounded tissue.